On October 26, AstraZeneca announced that its Phase III CAPItello-291 study of its AKT inhibitor Capivasertib in combination with Faslodex (fulvestrant) in breast cancer patients met the primary endpoint. Data show that Capivasertib plus Faslodex (fulvestrant) has a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in patients with locally advanced or metastatic breast cancer compared to placebo plus Faslodex.
Breast cancer is the most common cancer worldwide, with an estimated 2.3 million patients diagnosed in 2020. Approximately 70% of breast cancer tumours are considered HR-positive and HER2-low or negative. Endocrine therapies are widely used for the treatment of HR-positive breast cancer, but many patients with advanced disease develop resistance to 1st-line CDK4/6 inhibitors and estrogen receptor-targeting therapies, underscoring the need for additional options.
Capivasertib is an investigational oral treatment. Capivasertib is dosed according to an intermittent schedule, which consists of four days on and three days off. This was chosen in early phase trials based on tolerability and the degree of target inhibition.
CAPItello-291 is a Phase III, double-blind, randomised trial. The trial enrolled 708 adult patients, evaluating the efficacy of capivasertib in combination with Faslodex versus placebo plus Faslodex for the treatment of locally advanced (inoperable) or metastatic HR-positive, HER2-low or negative breast cancer.
The trial has dual primary endpoints of PFS in the overall patient population and in a subgroup of patients whose tumours have qualifying alterations in the PIK3CA, AKT1 or PTEN genes. In the trial, approximately 40% of tumours had PI3K/AKT/PTEN alterations.
The trial met both primary endpoints, improving PFS in the overall patient population and in a prespecified biomarker subgroup of patients whose tumours had qualifying alterations in the PIK3CA, AKT1 or PTEN genes. The safety profile of capivasertib plus Faslodex was similar to that observed in previous trials evaluating this combination.
